title: Insulin-like growth factor I affects the intraovarian interleukin-1 system: evidence for suppression of type I interleukin-1 receptor expression and enhancement of secretory phospholipase A2 expression and activity.
abstract: This study assessed the possibility that the intraovarian insulin-like growth factor I (IGF-I) system interacts with the intraovarian interleukin-1 (IL-1) system, the central role of which has been the subject of increasing attention. To this end, whole ovarian dispersates from immature rats were cultured for 48 h in the absence or presence of IGF-I or IGF-binding protein-3 (IGFBP-3), with or without IL-1beta. Cellular RNA content was subjected to a solution hybridization, RNase protection assay with gel-purified [32P]-UTP-labelled antisense riboprobes for rat IL-1beta, type I IL-1 receptor (IL-1R) and secretory phospholipase A2 (sPLA2). PLA2 activity in conditioned media was assayed by measuring the release of [3H]-labelled palmitic acid from the sn-2 position of [3H]-labelled phosphatidylcholine dipalmitoyl (PCDP) substrate. Treatment with IGF-I resulted in a significant (P< 0.01) decrease in type I IL-1R transcripts (an effect which was reversed by co-treatment with IL-1beta), was without effect on IL-1beta transcripts, and significantly (P < 0.05) increased sPLA2 gene expression (an effect which was further enhanced by co-treatment with IL-1beta). Treatment with IGF-I resulted in a significant increase in extracellular PLA2 activity over untreated control. These observations suggest that IGF-I may down-regulate ovarian IL-1 action by decreasing type I IL-1R gene expression, while up-regulating sPLA2 gene expression and activity. These findings are consistent with a role for IGF-I in suppressing IL-1 actions while promoting the generation of prostaglandins. It is tempting to speculate that IGF-I, an intraovarian regulator concerned with promoting folliculogenesis, may be also entwined with priming the prostaglandin-producing potential in anticipation of subsequent ovulation.
authors.affiliation: Department of Obstetrics and Gynecology, University of Maryland School of Medicine, Baltimore 21201, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kol
authors.forename: I
authors.initials: I
authors.lastname: Ben-Shlomo
authors.forename: M
authors.initials: M
authors.lastname: Ando
authors.forename: E Y
authors.initials: EY
authors.lastname: Adashi
mesh_terms: D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D005110:Extracellular Space / Q000187:drug effects / Q000201:enzymology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010741:Phospholipases A / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000187:drug effects*
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D017472:Receptors, Interleukin-1; D007334:Insulin-Like Growth Factor I; D010741:Phospholipases A; D054467:Phospholipases A2